Chen Jiaming, Cao Hongbao, Lian Meng, Fang Jugao
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
PeerJ. 2020 Jul 28;8:e9302. doi: 10.7717/peerj.9302. eCollection 2020.
Previous studies indicate that obesity is an important contributor to the proceeding of thyroid cancer (TC) with limited knowledge of the underlying mechanism. Here, we hypothesize that molecules affected by obesity may play roles in the development of TC. To test the hypothesis above, we first conducted a large-scale literature-based data mining to identify genes influenced by obesity and genes related to TC. Then, a mega-analysis was conducted to study the expression changes of the obesity-specific genes in the case of TC, using 16 independent TC array-expression datasets (783 TC cases and 439 healthy controls). After that, pathway analysis was performed to explore the functional profile of the selected target genes and their potential connections with TC. We identified 1,036 genes associated with TC and 534 regulated by obesity, demonstrating a significant overlap ( = 176, = 4.07e-112). Five out of the 358 obesity-specific genes, FABP4, CFD, GHR, TNFRSF11B, and LTF, presented significantly decreased expression in TC patients (LFC<-1.44; and < 1e). Multiple literature-based pathways were identified where obesity could promote the pathologic development of TC through the regulation of these five genes and INS levels. The five obesity genes uncovered could be novel genes that play roles in the etiology of TC through the modulation of INS levels.
先前的研究表明,肥胖是甲状腺癌(TC)进展的一个重要因素,但其潜在机制的相关知识有限。在此,我们假设受肥胖影响的分子可能在TC的发展中起作用。为了验证上述假设,我们首先进行了大规模的基于文献的数据挖掘,以确定受肥胖影响的基因和与TC相关的基因。然后,使用16个独立的TC阵列表达数据集(783例TC病例和439例健康对照)进行了一项荟萃分析,以研究肥胖特异性基因在TC病例中的表达变化。之后,进行通路分析以探索所选靶基因的功能概况及其与TC的潜在联系。我们鉴定出1036个与TC相关的基因和534个受肥胖调控的基因,显示出显著的重叠( = 176, = 4.07e-112)。358个肥胖特异性基因中的5个,即FABP4、CFD、GHR、TNFRSF11B和LTF,在TC患者中表达显著降低(LFC < -1.44;且 < 1e)。通过基于文献的多种通路分析发现,肥胖可通过调控这五个基因和胰岛素(INS)水平促进TC的病理发展。所发现的这五个肥胖相关基因可能是通过调节INS水平在TC病因学中发挥作用的新基因。